Ovariectomy and estrogen-induced alterations in myocardial contractility in female rabbits: role of the L-type calcium channel.
The effects of ovariectomy and estrogen replacement on myocardial contractility were examined in female rabbits. Ovariectomy failed to alter left ventricular mass, papillary muscle cross-sectional area or isometric force. Estrogen replacement after ovariectomy (0.15 microg/kg/day i.m. 17beta-estradiol acetate for 7 days) increased left ventricular mass and papillary muscle mass, and reduced isometric force compared to control and ovariectomy groups. Ovariectomy did not alter increased isometric force with isoproterenol, but decreased the ED50 for Bay K8644 (compared to control and estrogen groups). Estrogen replacement increased the ED50 for isoproterenol- and Bay K8644-induced isometric force compared to control and ovariectomy groups. Ovariectomy increased and estrogen replacement decreased isometric force associated with increased Ca++o. Acute exposure to 17beta-estradiol or diethylstilbesterol (10(-7) M, 10(-6) M) failed to alter isometric force in control papillary muscles. Estrogen replacement reduced the number, but not the dissociation constant for 3H-nitrendipine binding in plasma membrane preparations (compared to ovariectomy and control groups). Peak L-type calcium currents in isolated ventricular myocytes from the three treatment groups were not significantly different. The data are consistent with an ovariectomy-induced increase and estrogen-induced decrease in L-type calcium channel density in rabbit myocardium. Estrogen-induced alterations in L-type calcium channel expression and contractility are subsequently modified by estrogen-induced cardiac hypertrophy.
Patterson
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Department of Pharmacology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
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Szabo
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Robinson
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Thadani
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009568:Nitrendipine / Q000378:metabolism*; D010052:Ovariectomy; D010210:Papillary Muscles / Q000502:physiology; D011817:Rabbits; D013997:Time Factors
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D004958:Estradiol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004054:Diethylstilbestrol; D009568:Nitrendipine; D007545:Isoproterenol